Mechanistic exploration of quercetin against metronidazole induced neurotoxicity in rats: Possible role of nitric oxide isoforms and inflammatory cytokines.
Neurotoxicology
; 79: 1-10, 2020 07.
Article
in En
| MEDLINE
| ID: mdl-32151614
ABSTRACT
AIM:
Metronidazole, a nitroimidazole derived antibiotic used to treat many bacterial infections, is reported to penetrate the blood brain barrier after long term administration resulting into neuronal toxicity. Further, quercetin, a polyphenol flavonoid is reported to exhibit neuroprotective activity but its pharmacodynamics interaction against metronidazole induced neurotoxicity. Therefore, the present study was designed to evaluate the postulated mechanism of metronidazole induced neurotoxicity and potential neuroprotective role of quercetin. MAINMETHODS:
Animals (Sprague Dawley) rats were randomly divided into five groups such as control, metronidazole (135â¯mg/kg), quercetin (100â¯mg/kg), metronidazole (135â¯mg/kg) + quercetin (50â¯mg/kg), and metronidazole (135â¯mg/kg) + quercetin (100â¯mg/kg). The brain tissues were evaluated for tissue cyclo-oxygenase, lipoxygenase, nitrite levels, inflammatory and antioxidant biomarkers. The brain tissues were further scrutinized histopathologically for neuronal degeneration. Western blotting analysis was performed for the localization of protein expression for Bax, Bcl2, iNOS, eNOS and caspase-3. KEYFINDINGS:
The metronidazole significantly alters the antioxidant levels, inflammatory mediators and morphological changes in the brain tissue. Metronidazole also induces iNOS, Bax and caspase 3 protein expressions whilst decreases the expression of Bcl2 and eNOS in the brain tissue. Metronidazole administration causes a momentous increase in tissue inflammatory markers.SIGNIFICANCE:
The metronidazole (oral) administration causes remarkably neurotoxicity effects and the same could be attributed to the fact that metronidazole has the ability to cross the blood brain barrier and transforms the enzymatic activity of various biomarkers present in the brain. From the results, it could be hypothesized that metronidazole causes neurotoxicity by hindering the proportion of antioxidants in the brain tissue and inducing nitric oxide synthesis along with apoptosis. However, quercetin demonstrated a significant protective effect on neuronal toxicity precipitated through metronidazole.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Quercetin
/
Brain
/
Cytokines
/
Neuroprotective Agents
/
Inflammation Mediators
/
Neurotoxicity Syndromes
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Nitric Oxide Synthase Type II
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Nitric Oxide Synthase Type III
/
Anti-Inflammatory Agents
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Neurotoxicology
Year:
2020
Document type:
Article
Affiliation country:
India